Dr Ahmad Allouche, Head of in vitro biology, presented the team’s research* during AD/PD 2025 in Vienna in his poster “ADVANCING ALZHEIMER’S DISEASE MODELS FOR PRECLINICAL DRUG TESTING“.
Learn more about our cutting-edge platform for target identification & drug discovery in the poster!
Authors: *Ahmad ALLOUCHE, Valentin TALLANDIER, Sonia KRIDI, Léane DIER, Julie COLIN, Nicolas VIOLLE
Affiliates: ETAP-Lab, 54500, Vandœuvre-lès-Nancy, France
Abstract:
Though Alzheimer’s disease (AD) is the most common cause of dementia, complete disease-modifying treatments are yet to be fully attained. The development and commercialization of new drugs is a lengthy and very expensive process and current approaches targeting the too-late stages of AD have had no consistent clinical benefit. For this reason, development of predictive and robust preclinical models, recapitulating early neuropathological features of AD are of urgent need. Here, we report the progress in our development of high throughput in vitro models that captures AD characteristics using physiopathologically relevant culture conditions.
Assessment of cellular phenotypic changes (neurons or glial cells from rodent or human induced pluripotent stem cells (iPSCs) induced after an exposure of human amyloid oligomers (AβO and TauO) were performed using 2D-cultures, brain-on-chip (BoC) models, and a high content imaging system. These oligomeric preparations were prepared in-house from human Aβ1-42 and Tau (2N4R) monomers and were well-characterized by various methods (SDS-page, dot-blot, 8-Anilino-1-NaphthaleneSulfonic acid (ANS) and Sedimentation Velocity Analytical Ultracentrifugation (SV-AUC) assays).
Our data showed that increasing concentrations of oligomers have been associated with significantly loss of synaptic markers, reduction of neurite outgrowth and ultimately neuron death. They also triggered neuroinflammatory processes via activation of astrocytes. Induced neurodegeneration and neuroinflammation were successfully attenuated by pharmacologic compounds, including monoclonal antibodies, which have produced encouraging therapeutic results in clinical trials.
In conclusion, we characterized many experimental situations to better understand the mechanisms underlying AD, and targeting oligomers or their harmful effects which should give rise to new therapeutic interventions. Complexifying of in vitro models, combining neuron and glia, using BoC devices and targeting both amyloid and tau for development next generation AD prevention could be of great interest.
